How tenofovir disoproxil fumarate can impact on solubility and dissolution rate of efavirenz?

• Published in: International journal of pharmaceutics 2019-10, Vol.570, p.118597-118597, Article 118597
• Main Authors: Bazzo, Giovana Carolina, Mostafa, Dina, França, Maria Terezinha, Pezzini, Bianca Ramos, Stulzer, Hellen Karine
• Format: Article
• Language: English
• Subjects: Benzoxazines - chemistry; Calorimetry, Differential Scanning - methods; Dissolution; Efavirenz; Eutectic mixture; Powders - chemistry; Solubility; Solubility - drug effects; Spectroscopy, Fourier Transform Infrared; Tenofovir - chemistry; Tenofovir disoproxil fumarate; X-Ray Diffraction - methods
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.118597

[Display omitted] Efavirenz (EFZ) and tenofovir disoproxil fumarate (TDF) can be used simultaneously in the treatment of human immunodeficiency virus type1 infection. In this work the impact of TDF, a hydrophilic drug, on the solubility and dissolution rate of EFZ, a poorly water-soluble drug, was evaluated. EFZ/TDF binary mixtures in different molar ratios were prepared. Differential scanning calorimetry (DSC) results indicate the formation of a eutectic mixture, the molar ratio of 65/35 being the eutectic point. It was observed an increase in the EFZ solubility in water and acidic conditions (0.1 N HCl and biorelevant medium), in the presence of TDF. On the other hand, there was a decreasing on EFZ solubility in phosphate buffer pH 6.8, probably influenced by the lower solubility of TDF in this medium. The high solubility of TDF in water and acidic medium may have contributed to improve the solubility of EFZ, as well as the formation of a eutectic mixture, supported by X-ray powder diffraction (XRPD) and Fourier Transform infrared spectroscopy (FTIR) analyses. However, TDF solubility and dissolution rate was not significantly influenced by the presence of EFZ.